Gene therapy is a powerful technology for treatment of a variety of diseases. The earliest applications of gene therapy were based on the principle that when a disease is caused by a faulty gene or combination of genes, the disease might be controlled, prevented or cured by replacement of the faulty gene with a functional version. Gene therapy has been applied to many different genetic diseases in this context, including ADA deficiency, familial hypercholesterolaemia and cystic fibrosis. Several clinical trials employing gene therapy protocols have already been completed with some success in patients, although the effectiveness of the protocols can be limited by the inefficiency of the gene transfer vectors. Gene therapy has also been applied to a variety of protocols that involve an element of gene transfer, but which do not involve correction of a genetic defect.
Methods for the transfer of foreign genes into eukaryotic cells are essential to the development of gene therapy strategies. To this end, different mammalian expression vector systems have been designed. The choice of a particular expression system depends on the nature and purpose of the study and involve selecting particular parameters of expression systems such as the type of promoter/enhancer sequences, the type of expression (transient versus stable) and the level of desired expression. In addition to the vector itself, the formulation of the nucleic acid for in vivo delivery must be considered. Numerous approaches have been developed to facilitate the transfer of genes into cells via physical, chemical or viral strategies. While these systems have all been effective in vitro they do not necessarily lead to effective in vivo transfection.
Although liposome DNA delivery systems have been assessed in gene therapy clinical trials, there are concerns about inefficiency of liposome-based gene transfer technology. While many approaches have been taken to improve transfection efficiency, because of the complex nature of the formulation technology it is difficult to define specific carrier attributes that enhance transfection.
Methods of gene delivery in vivo that provide for efficient and targeted delivery of the desired sequence are of great interest for clinical and scientific uses. The present invention addresses this issue.